Interaction of Cationic Nickel and Manganese Porphyrins with the Minor Groove of DNA
- 17 August 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Inorganic Chemistry
- Vol. 49 (18), 8558-8567
- https://doi.org/10.1021/ic101178n
Abstract
The capacity of a series of new cationic nickel and manganese metalloporphyrins to bind in the minor groove of DNA was evaluated by binding competition experiments with manganese(III)-bis-aqua-meso-tetrakis(4-N-methylpyridiniumyl)porphyrin, Mn-TMPyP, a powerful artificial nuclease when associated with KHSO5. The four N-methylpyridiniumyl substituents on this porphyrin macrocycle are responsible for a strong binding affinity for the minor groove of AT-rich DNA. The inhibition of DNA cleavage mediated by Mn-TMPyP/KHSO5 by the various tested porphyrins correlated with their competitive occupancy of the minor groove site of Mn-TMPyP. Introduction of long and flexible cationic substituents at the periphery of the porphyrin macrocycle precluded the interaction of the porphyrin derivative in the minor groove and resulted in low affinity for DNA. On the other hand, introduction of phenylpyridiniumyl substituents on the porphyrin macrocycle surprisingly conferred the new porphyrin derivative with a tight binding in the minor groove of a six consecutive AT base pairs sequence. These data on structural requirements for minor groove DNA binding will help the rational design of porphyrin derivatives for selective targeting of quadruplex DNA versus double-stranded DNA.Keywords
This publication has 52 references indexed in Scilit:
- Asymmetrically substituted cationic indole- and fluorene porphyrins inhibit tumor proliferation in small intestinal neuroendocrine tumors and medullary thyroid carcinomasEuropean Journal of Medicinal Chemistry, 2010
- Cationic N-confused porphyrin derivative as a better molecule scaffold for G-quadruplex recognitionBioorganic & Medicinal Chemistry, 2010
- Steric effects direct the binding of porphyrins to tetramolecular quadruplex DNAChemical Communications, 2009
- A Role for Water Molecules in DNA−Ligand Minor Groove RecognitionAccounts of Chemical Research, 2008
- Long-range charge transport through double-stranded DNA mediated by manganese or iron porphyrinsJBIC Journal of Biological Inorganic Chemistry, 2008
- End-stacking of copper cationic porphyrins on parallel-stranded guanine quadruplexesJBIC Journal of Biological Inorganic Chemistry, 2007
- Guanine Oxidation: One‐ and Two‐Electron ReactionsChemistry – A European Journal, 2006
- G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcriptionNucleic Acids Research, 2006
- Porphyrin Derivatives for Telomere Binding and Telomerase InhibitionChemBioChem, 2005
- Quantitative footprinting analysis using a DNA-cleaving metalloporphyrin complexBiochemistry, 1989